The current work examines the expression of acute phase genes in a murine-derived bone marrow stromal cell model (BMS2) which exhibits adipocyte and osteoblast characteristics and supports lymphopoiesis in vitro. Each of these physiologic processes is responsive to inflammatory events such as endotoxemia. Exposure of BMS2 cells to pro-inflammatory cytokines induced the expression of the serum amyloid A and complement factor B. During adipocyte differentiation, expression of complement C3, complement factor D (adipsin), and angiotensinogen increased in a time dependent manner. The bone metabolic steroid, 1,25 dihydroxy vitamin D3, specifically induced complement C3 expression in a time- and dose-dependent manner. Based on gel retention analysis, BMS2 nuclear extract contained proteins recognizing specific response elements from the complement C3, angiotensinogen, and complement factor B promoters. These results suggest that the bone marrow's repertoire of acute phase proteins is dependent on the stromal cell's phenotype or activation state.
Baumann H., Gauldie J.Regulation of hepatic acute plasma protein genes by hepatocyte stimulating factors and mediators of inflammation. Mol Biol Med1990; 7: 147-159.
3.
Lappin D.F., Whaley K.Modulation of complement gene expression by glucocorticoids. Biochem J1991 ; 280: 117-123.
4.
Passwell J.H. , Schreiner G.F., Wetsel R.A., Colten H.R.Complement gene expression in hepatic and extrahepatic tissues of NZB and NZB/W(F1) mouse strains. Immunology1990; 71: 290-294.
5.
Choy L.N., Rosen R.S., Spiegelman B.M.Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem1992; 267: 12736-12741.
6.
Rosen B.S., Cook K.S., Yaglom J. et al. Adipsin and complement factor D activity: an immune-related effect in obesity. Science1992; 244: 1483-1485.
7.
Saye J.A., Cassis LA, Sturgill T.W., Lynch K.R., Peach M.J.Angiotensinogen gene expression in 3T3-L1 cells. Am J Physiol1989; 256: C448-C451.
8.
Saye J., Lynch K.R., Peach M.J.Changes in angiotensinogen messenger RNA in differentiating 3T3-F442A adipocytes . Hypertension1990; 15: 867-871.
9.
Hong M.E., Jin C.H., Sato T., Ishimi Y., Abe E., Suda T.Transcriptional regulation of the production of the third component of complement (C3) by 1, alpha 25-dihydroxyvitamin D3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells. Endocrinology1991; 129: 2774-2779.
10.
Sato T., Hong M.H., Jin C.H. et al. The specific production of the third component of complement by osteoblastic cells treated with 1 alpha, 25-dihydroxyvitamin D3. FEBS Lett1991; 285: 21-24.
11.
Bennett Jr I.L., Beeson P.B.The properties and biologic effects of bacterial pyrogens. Medicine1950; 29: 365-400.
12.
Mechanic R.C. , Frei III E., Landy M., Smith W.W.Quantitative studies of human leucocytic and febrile response to single and repeated doses of purified bacterial endotoxin . J Clin Invest1961; 41: 162-172.
13.
Kincade P.W. , Lee G., Pietrangeli C.E., Hayashi S-I., Gimble J.M.Cells and molecules that regulate B lymphopoiesis in bone marrow. Annu Rev Immunol1988 ; 7: 111-143.
14.
Deryugina E.I. , Müller-Sieburg C.E.Stromal cells in long-term cultures: keys to the elucidation of hematopoietic development?Crit Rev Immunol1993; 13: 115-150.
15.
Lerner U.H.Regulation of bone metabolism by the kallikreinkinin system, the coagulation cascade, and the acute-phase reactants. Oral Surg Oral Med Oral Pathol1994; 78: 481-493.
16.
Suda T., Takahashi N., Abe S.Role of vitamin D in bone resorption. J Cell Biochem1992; 49: 53-58.
17.
Sato T., Abe E., Jin C.H. et al. The biological roles of the third component of complement in osteoclast formation. Endocrinology1993; 133: 397-404.
18.
Jin C.H., Shinki T., Hong M.H. et al. 1α,25-dihydroxyvitamin D3 regulates in vivo production of the third component of complement (C3) in bone. Endocrinology1992; 131: 2468-2475.
19.
Pietrangeli C.E., Hayashi S-I., Kincade P.W.Stromal cell lines which support lymphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors. Eur J Immunol1988; 18: 863-872.
20.
Gimble J.M. , Hudson J., Henthorn J.H., Hua X., Burstein S.A.Regulation of interleukin 6 expression in murine bone marrow stromal cells. Exp Hematol1991; 19: 1055-1060.
21.
Dorheim M.A. , Sullivan M., Dandapani V. et al. Osteoblastic gene expression during adipogenesis in hemopoietic supporting murine bone marrow stromal cells. J Cell Physiol1992; 154(2): 317-328.
22.
Gimble J.M.The function of adipocytes in the bone marrow stroma. New Biol1990; 2: 304-312.
23.
Gimble J.M. , Dorheim M-A., Cheng Q. et al. Response of bone marrow stromal cells to adipogenic antagonists. Mol Cell Biol1989 ; 9: 4587-4595.
24.
Anklesaria P., Klassen V., Sakakeeny M.A. et al. Biological characterization of cloned permanent stromal cell lines from anemic Sl/Sld mice and +/+ littermates. Exp Hematol1987; 15: 636-644.
25.
Gimble J.M. , Youkhana K., Hua X. et al. Adipogenesis in a myeloid supporting bone marrow stromal cell Line. J Cell Biochem1992; 50: 73-82.
26.
Chomczynski P., Sacchi N.Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem1987; 162: 156-159.
27.
Thomas P.S.Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA1990; 77: 5201-5205.
Feinberg A.P. , Vogelstein B.A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem1983; 132: 6-13.
30.
Domdey H., Wiebauer K., Kazmaier M., Muller V., Odink K., Fey G.Characterization of the mRNA and cloned cDNA specifying the third component of mouse complement. Proc Natl Acad Sci USA1982; 79: 7619-7623.
31.
Sackstein R. , Colten H.R.Molecular regulation of MHC class III (C4 and factor B) gene expression in mouse peritoneal macrophages. J Immunol1984; 133: 1618-1626.
32.
Wetsel R.A. , Lemons R.S., Le Beau M.M., Barnum S.R., Noack D., Tack B.F.Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9. Biochemistry1988; 27: 1474-1482.
33.
Falus A., Beuscher H.U., Auerbach H.S., Colten H.R.Constitutive and IL 1-regulated murine complement gene expression is strain and tissue specific. J Immunol1987; 138: 856-860.
34.
Lynch K.R., Simnad V.I., Ben-Ari E.T., Garrison J.C. Localization of preangiotensinogen messenger RNA sequences in the rat brain. Hypertension1986 ; 8: 540-543.
35.
Webb C.F., Tucker P.W., Dowton S.B.Expression and sequence analyses of serum amyloid A in the Syrian hamster . Biochemistry1989; 28: 4785-4790.
36.
Wilkinson W.O. , Min H.Y., Claffey K.P., Satterberg B.L., Spiegelman B.M.Control of the adipsin gene in adipocyte differentiation: identification of distinct nuclear factors binding to single- and double-stranded DNA. J Biol Chem1990; 265: 477-482.
37.
Harpold M.M. , Evans R.M., Salditt-Georgieff M., Darnell J.E.Production of mRNA in Chinese hamster cells: relationship of the rate of synthesis to the cytoplasmic concentration of nine specific mRNA sequences. Cell1979; 17: 1025-1035.
38.
Wilson D.R. , Juan T.S-C. , Wilde M.D., Fey G.H., Darlington G.J.A 58-basepair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukin-6. Mol Cell Biol1990 ; 10: 6181-6191.
39.
Nonaka M., Huang Z-M.Interleukin-1-mediated enhancement of mouse factor B gene expression via NFκB-like hepatoma nuclear factor. Mol Cell Biol1990 ; 10: 6283-6289.
40.
Brasier A.R. , Ron D., Tate J.E., Habener J.F. A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced, NFκB mediated trans-activation of the angiotensinogen gene acute-phase response element. EMBO J1990; 9: 3933-3944.
41.
Hua X., Enerback S., Hudson J., Youkhana K., Gimble J.M.Cloning and characterization of the promoter of the murine lipoprotein lipase-encoding gene: structural and functional analysis. Gene1991; 107: 247-258.
42.
Dignam J.M. , Martin P.L., Shastry B.S., Roeder R.G.Eukaryotic gene transcription with purified components. Methods Enzymol1983; 101: 582-598.
43.
Gimble J.M. , Flanagan J.R., Recker D., Max H.H.Identification and partial purification of a protein binding to the human immunoglobulin κ enhancer kE2 site. Nucleic Acids Res1988; 16: 4967-4988.
44.
Landolfi N.F. , Capra J.D., Tucker P.W.Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature1986; 323: 548-551.
45.
Rigby W.F.C.The immunobiology of vitamin D. Immunol Today1988; 9: 54-58.
46.
Sato H., Hiragun A.Demonstration of 1 alpha, 25dihydroxyvitamin D3 receptor-like molecule in ST 13 and 3T3 L1 preadipocytes and its inhibitory effects on preadipocyte differentiation. J Cell Physiol1988 ; 135: 1540-1550.
47.
Shionome H., Shinski T., Takahashi N., Hasegawa K., Suda T.1 alpha, 25-dihydroxyvitamin D3 modulation in lipid metabolism in established bone marrow-derived stromal cells, MC3T3-G2/PA6. J Cell Biochem1992; 48: 424-430.
48.
Campbell R.D. , Law S.K.A., Reid K.B.M., Sim R.B.Structure, organization, and regulation of complement genes. Annu Rev Immunol1988 ; 6: 161-195.
49.
Lambris J.D.The multifunctional role of C3, the third component of complement. Immunol Today1988; 9: 387-393.
50.
Sundstrom S.A. , Komm B.S., Ponce-de-Leon H., Yi Z., Teuscher C., Lyttle C.R.Estrogen regulation of tissue-specific expression of complement. J Biol Chem1989; 264: 16941 - 16947.
51.
Zach T.L., Hill L.D., Herrman VA, Leuschen H.P., Hostetter H.K.Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line. J Immunol1992; 148: 3964-3969.
52.
Erdei A., Helchers F., Schulz T., Dierich H.The action of human C3 in soluble and cross-linked form with resting and activated murine B lymphocytes. Eur J Immunol1985 ; 15: 184-188.
53.
Helchers F. , Erdel A., Schultz T., Dierich M.P.Growth control of activated, synchronized murine B cells by the C3d fragment of human complement. Nature1985; 317: 264-267.
54.
Hebell T., Ahearn J.H., Fearon D.T.Suppression of the immune response by a soluble complement receptor of B lymphocytes . Science1991; 254: 102-105.
55.
McKnight S.L. , Lane H.D., Gluecksohn-Waelsch S.Is CCAAT/enhancer-binding protein a central regulator of energy metabolism?Genes Dev1989; 3: 2021-2024.
56.
Christy R.J. , Yang V.W., Ntambi J.M. et al. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev1989; 3: 1323-1335.
57.
Kaestner K.H. , Christy R.J., Lane H.D.M.Mouse insulin-responsive glucose transporter gene: characterization of the gene and trans-activation by the CCAAT/enhancer binding protein. Proc Natl Acad Sci USA1990 ; 87: 251-255.
58.
Friedman A.D. , Landschulz W.H., McKnight S.L.C/EBP activates the serum albumin promoter in cultured hepatoma cells. Genes Dev, 1989 ; 3(9): 1314-1322.
59.
Isihiki H., Akira S., Sugita T. et al. Reciprocal expression of NF-1L6 and C/EBP in hepatocytes: possible involvement of NE-IL6 in acute phase protein gene expression. New Biol1991; 3: 63-70.
60.
Campos S.P. , Baumann H.Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes. Mol Cell Biol1992; 12: 1789-1797.
61.
Cao I., Umek S.M., McKnight S.L.Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev1991; 5: 1538-1552.
62.
Li X., Huang J.H., Rienhoff H.Y., Liao W.S-L. No adjacent C/EBP-binding sequences that participate in the cell-specific expression of the mouse serum amyloid A3 gene. Mol Cell Biol1990 ; 10: 6624-6631.
63.
Ramji D.P., Vitelli A., Tronche F., Cortese R., Ciliberto G.The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBPδ/NF-IL6β, are induced by IL-6 to promote acute phase gene transcription via different mechanisms . Nucleic Acids Res1993; 21: 289-294.
64.
Akira S., Kishimoto T.IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev1992; 127: 25-50.
65.
Baumann H., Morella K.K., Campos S.P., Cao Z., Jahreis G.P.Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of acute-phase plasma protein genes. J Biol Chem1992;267: 19744-19751.
66.
Alam T., An M.R., Papaconstantinou J.Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. J Biol Chem1992 ; 267: 5021-5024.
67.
Juan T.S-C , Wilson D.R., Wilde M.D., Darlington G.J.Participation of the transcription factor C/EBPδ in the acute-phase regulation of the human gene for complement component C3. Proc Natl Acad Sci USA1993; 90: 2584-2588.
